Analysis and projections of disease burden for different risk factors and sexes of ischemic stroke in young adults in China.

To estimate the rate of death, and disability-adjusted life years (DALYs) and project the disease burden of ischemic stroke due to relevant risk factors in young adults age 20-49 years by sex in China. Data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The age-standardized mortality (ASMR), age-standardized DALYs rate (ASDR), and estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trends from 1990 to 2019. We also used the NORDPRED model to predict ASMR for ischemic stroke due to related risk factors in Chinese young adults over the next 10 years. From 1990 to 2019, the general age-standardized mortality [from 2.39 (1.97 to 2.99) in 1990 to 1.8 (1.41 to 2.18) in 2019, EAPC = - 1.23] and DALYs rates (from 171.7 (140.34 to 212.36) in 1990 to 144.4 (114.29 to 177.37) in 2019, EAPC = - 0.86) decreased for ischemic stroke in young adults in China. ASMR and ASDR decreased for all level 1 risk factors (including behavioral, environmental/occupational, and metabolic) from 1990 to 2019, with the slightest decrease for metabolic risks [ASMR from 1.86 (1.39 to 2.41) in 1990 to 1.53 (1.15 to 1.92) in 2019, ASDR from 133.68 (99.96 to 173.89) in 1990 to 123.54 (92.96 to 156.98) in 2019] and the largest decrease for environmental/occupational risks [ASMR from 1.57 (1.26 to 1.98) in 1990 to 1.03 (0.78 to 1.29) in 2019, ASDR from 110.91 (88.44 to 138.34) in 1990 to 80.03 (61.87 to 100.33) in 2019]. In general, high body-mass index, high red meat intake, and ambient particulate matter pollution contributed to the large increase in ASMR and ASDR between 1990 and 2019. Significant reductions in ASMR and ASDR were observed in low vegetables intake, household air pollution from solid fuels, lead exposure, and low fiber intake. In addition, there were sex differences in the ranking of ASMR attributable to risks in ischemic stroke. The disease burden of ischemic stroke attributable to relevant risk factors in young adults in China is greater and has a faster growth trend or a slower decline trend in males than in females (except for secondhand smoke). The apparent increasing trend of ASMR attributable to high fasting plasma glucose, high systolic blood pressure, high body-mass index, and high red meat intake was observed in males but not in females. The projected analysis showed an increasing trend in ASMR between 1990 and 2030 for all specific metabolic risks for males, but a decreasing trend for females. ASMR attributable to ambient particulate matter pollution showed an increasing trend from 1990 to 2030 for both males and females. The burden of ischemic stroke in young adults in China showed a downward trend from 1990 to 2019. Specific risk factors associated with the burden of ischemic stroke varied between the sexes. Corresponding measures need to be developed in China to reduce the disease burden of ischemic stroke among young adults.

Prediction of mechanical ventilation in Guillain-Barré syndrome at admission: Construction of a nomogram and comparison with the EGRIS model.

Background: Respiratory failure requiring mechanical ventilation (MV) is a common and severe complication of Guillain-Barré syndrome (GBS) with a reported incidence ranging from 20 % to 30 %. Thus, we aim to develop a nomogram to evaluate the risk of MV in patients with GBS at admission and tailor individualized care and treatment. Methods: A total of 633 patients with GBS (434 in the training set, and 199 in the validation set) admitted to the First Hospital of Jilin University, Changchun, China from January 2010 to January 2021 were retrospectively enrolled. Subjects (n = 71) from the same institution from January 2021 to May 2022 were prospectively collected and allocated to the testing set. Multivariable logistic regression analysis was applied to build a predictive model incorporating the optimal features selected in the least absolute shrinkage and selection operator (LASSO) in the training set. The predictive model was validated using internal bootstrap resampling, an external validation set, and a prospective testing set, and the model's performance was assessed by using the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Finally, we established a multivariable logistic model by using variables of the Erasmus GBS Respiratory Insufficiency Score (EGRIS) and did the same analysis to compare the performance of our predictive model with the EGRIS model. Results: Variables in the final model selected by LASSO included time from onset to admission, facial and/or bulbar weakness, Medical Research Council sum score at admission, neutrophil-to-lymphocyte ratio, and platelet-lymphocyte ratio. The model presented as a nomogram displaying favorable discriminative ability with a C-index of 0.914 in the training set, 0.903 in the internal validation set, 0.953 in the external validation set, and 0.929 in the testing set. The model was well-calibrated and clinically useful as assessed by the calibration curve and DCA. As compared with the EGRIS model, our predictive model displayed satisfactory performance. Conclusions: We constructed a nomogram for early prediction of the risk of MV in patients with GBS. This model had satisfactory performance and appeared more efficient than the EGRIS model in Chinese patients with GBS.

Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.

Introduction: The ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer's disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment. Methods: Fourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann-Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers. Results: Regarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers. Conclusion: APOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.

Associations of Serum Liver Function with Cerebral Blood Flow in Patients with Alzheimer's Disease.

Background: Increasing evidence suggests that both amyloid-ß metabolism disorders in the liver and cerebral hypoperfusion play an important role in the pathogenesis of Alzheimer's disease (AD). However, the relevance of liver function alterations to cerebral blood flow (CBF) of patients with AD remains unclear. Objective: We aimed to investigate the associations between liver function changes and CBF of patients with AD. Methods: We recruited 17 patients with sporadic AD. In addition to physical and neurological examinations, detection of AD biomarkers in cerebrospinal fluid by enzyme-linked immunosorbent assay and CBF assessment by arterial spin labeling sequence of magnetic resonance image scans as well as measure of liver function markers in serum by routine laboratory testing were conducted. Neuropsychological tests were evaluated, including Mini-Mental State Examination and Montreal Cognitive Assessment. Linear and rank correlations were performed to test the associations of liver function alterations with regional CBF of AD. Results: We found that liver function markers, especially total protein, the ratio of albumin to globin, globin, alkaline phosphatase, and aspartate aminotransferase were significantly associated with regional CBF of AD patients. Conclusions: These findings demonstrated significant associations between perfusion in certain brain regions of AD and alterations of liver function markers, particularly proteins and liver enzymes, which might provide implications to the pathogenesis and treatment of AD.

Phospholipase D, a Novel Therapeutic Target Contributes to the Pathogenesis of Neurodegenerative and Neuroimmune Diseases.

Phospholipase D (PLD) is an enzyme that consists of six isoforms (PLD1-PLD6) and has been discovered in different organisms including bacteria, viruses, plants, and mammals. PLD is involved in regulating a wide range of nerve cells' physiological processes, such as cytoskeleton modulation, proliferation/growth, vesicle trafficking, morphogenesis, and development. Simultaneously, PLD, which also plays an essential role in the pathogenesis of neurodegenerative and neuroimmune diseases. In this review, family members, characterizations, structure, functions and related signaling pathways, and therapeutic values of PLD was summarized, then five representative diseases including Alzheimer disease (AD), Parkinson's disease (PD), etc. were selected as examples to tell the involvement of PLD in these neurological diseases. Notably, recent advances in the development of tools for studying PLD therapy envisaged novel therapeutic interventions. Furthermore, the limitations of PLD based therapy were also analyzed and discussed. The content of this review provided a thorough and reasonable basis for further studies to exploit the potential of PLD in the treatment of neurodegenerative and neuroimmune diseases.

Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP).

Glial fibrillary acidic protein (GFAP), an intracellular type III intermediate filament protein, provides structural support and maintains the mechanical integrity of astrocytes. It is predominantly found in the astrocytes which are the most abundant subtypes of glial cells in the brain and spinal cord. As a marker protein of astrocytes, GFAP may exert a variety of physiological effects in neurological diseases. For example, previous published literatures showed that autoimmune GFAP astrocytopathy is an inflammatory disease of the central nervous system (CNS). Moreover, the studies of GFAP in brain tumors mainly focus on the predictive value of tumor volume. Furthermore, using biomarkers in the early setting will lead to a simplified and standardized way to estimate the poor outcome in traumatic brain injury (TBI) and ischemic stroke. Recently, observational studies revealed that cerebrospinal fluid (CSF) GFAP, as a valuable potential diagnostic biomarker for neurosyphilis, had a sensitivity of 76.60% and specificity of 85.56%. The reason plasma GFAP could serve as a promising biomarker for diagnosis and prediction of Alzheimer's disease (AD) is that it effectively distinguished AD dementia from multiple neurodegenerative diseases and predicted the individual risk of AD progression. In addition, GFAP can be helpful in differentiating relapsing-remitting multiple sclerosis (RRMS) versus progressive MS (PMS). This review article aims to provide an overview of GFAP in the prediction of clinical progression in neuroinflammation, brain tumors, TBI, ischemic stroke, genetic disorders, neurodegeneration and other diseases in the CNS and to explore the potential therapeutic methods.

Changing Patterns of Stroke and Subtypes Attributable to High Systolic Blood Pressure in China From 1990 to 2019.

BACKGROUND: It is unknown whether high systolic blood pressure had a similar effect on the disease burden of stroke subtypes. The aim of our study is to compare the long-term trends of stroke subtypes and sex groups attributable to high systolic blood pressure in China from 1990 to 2019. METHODS: Data about the age-standardized mortality rate and the age-standardized disability-adjusted life-year rate of stroke subtypes attributable to high systolic blood pressure in China were extracted in GBD (Global Burden of Disease) 2019. The trends in the age-standardized mortality rate and the age-standardized disability-adjusted life-year rate were calculated using the liner regression and age-period-cohort method, adjusted for age, period, and cohort. RESULTS: The estimated annual percentage change for mortality of stroke attributable to high systolic blood pressure was different from subtypes, with an estimated annual percentage change and 95% CI of 0.56 (0.37-0.74) for ischemic stroke (IS), -1.52 (-1.97 to -1.07) for intracerebral hemorrhage, and -7.02 (-7.86 to -6.17) for subarachnoid hemorrhage (SAH). The curve of the net drifts showed a downward trend for intracerebral hemorrhage and SAH, but that showed a stable trend for IS. The curve of local drifts showed a slow upward trend with age for IS, a slow downward trend for intracerebral hemorrhage, and a sharp downward trend for SAH. The drift curves showed different trends for males and females. The proportion of stroke mortality in young males was gradually increasing. The cohort rate ratio varied by subtypes, with the greatest decline for SAH, a slight decrease for intracerebral hemorrhage, and a slight increase for IS. The period rate ratio had decreased over the past 3 decades, with the greatest decline for SAH and the weakest decrease for IS. Moreover, both the period and cohort rate ratios for IS mortality due to high systolic blood pressure in males have increased significantly over the past 3 decades. CONCLUSIONS: Our results provided strong evidence that the disease burden of stroke attributable to high systolic blood pressure varied by subtypes and sex in China from 1990 to 2019. The age-standardized mortality rate and the age-standardized disability-adjusted life-year rate decreased for hemorrhagic stroke but increased for IS. Males had a higher mortality and exposure risk but a slighter decreasing trend than females. Our study suggested that greater attention should be given to the prevention of the burden of IS attributable to systolic blood pressure in China, especially for males.

Gut flora in multiple sclerosis: implications for pathogenesis and treatment.

ABSTRACT: Multiple sclerosis is an inflammatory disorder characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Although current first-line therapies can help manage symptoms and slow down disease progression, there is no cure for multiple sclerosis. The gut-brain axis refers to complex communications between the gut flora and the immune, nervous, and endocrine systems, which bridges the functions of the gut and the brain. Disruptions in the gut flora, termed dysbiosis, can lead to systemic inflammation, leaky gut syndrome, and increased susceptibility to infections. The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors, and gut flora may play a pivotal role in regulating immune responses related to multiple sclerosis. To develop more effective therapies for multiple sclerosis, we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis. This review provides an overview of the role of the gut flora in multiple sclerosis.

Current non-invasive strategies for brain drug delivery: overcoming blood-brain barrier transport.

BACKGROUND: The blood-brain barrier (BBB) is a complex and dynamic structure that serves as a gatekeeper, restricting the migrations of most compounds and molecules from blood into the central nervous system (CNS). The BBB plays a crucial role in maintaining CNS physiological function and brain homeostasis. It can protect the CNS from the entrance of toxic and infectious agents, however, it also restricts the drug permeation into brain to play a therapeutic role. The BBB has been the biggest limiting hurdle to medications entering the brain excluding from the brain about 100% of large-molecule and more than 98% of all small-molecule neurotherapeutics. As a result, it is of inability for drug molecule to reach requisite concentrations within the brain. OBJECTIVE: With the aim of enhancing drug permeability and efficacy, a variety of strategies have been developed: invasive approaches, such as intraarterial delivery, intrathecal delivery, or administrating directly the drug intraventricularly and intracerebrally; non-invasive approaches that take advantage of innate BBB functions, using prodrugs, focused ultrasound, intranasal administration or nanotechnology. CONCLUSIONS: Here we mainly review recent developments and challenges related to non-invasive BBB-crossing techniques, whose benefits include higher efficacy, easier application, less treatment burden, better patient acceptability, and adherence. Additionally, we also analyze the potential of non-invasive methods in the treatment of CNS disorders and render them as a most suitable platform for the management of neurological diseases.

Glymphatic system: an emerging therapeutic approach for neurological disorders.

The functions of the glymphatic system include clearance of the metabolic waste and modulation of the water transport in the brain, and it forms a brain-wide fluid network along with cerebrospinal fluid (CSF) and interstitial fluid (ISF). The glymphatic pathway consists of periarterial influx of CSF, astrocyte-mediated interchange between ISF and CSF supported by aquaporin-4 (AQP4) on the endfeet of astrocyte around the periarterioles, and perivenous efflux of CSF. Finally, CSF is absorbed by the arachnoid granules or flows into the cervical lymphatic vessels. There is growing evidence from animal experiments that the glymphatic system dysfunction is involved in many neurological disorders, such as Alzheimer's disease, stroke, epilepsy, traumatic brain injury and meningitis. In this review, we summarize the latest progress on the glymphatic system and its driving factors, as well as changes in the glymphatic pathway in different neurological diseases. We significantly highlight the likely therapeutic approaches for glymphatic pathway in neurological diseases, and the importance of AQP4 and normal sleep architecture in this process.

The effects of high plasma levels of Aß1-42 on mononuclear macrophage in mouse models of Alzheimer's disease.

More and more evidences are proving that microglia play a crucial role in the pathogenesis of Alzheimer's disease (AD) and the plasma Aß1-42 levels significantly increased 15 years before the onset of dominantly inherited AD. However, the effects of high plasma levels of Aß1-42 on mononuclear macrophage, the peripheral counterparts of microglia, remain unclear. In the present study, we used APP/PS1 transgenic (Tg) mice and a parabiotic model of wild type (Wt) mice and Tg mice (Parabiotic Wt-Tg, Pa (Wt-Tg)) to investigate the effects of high plasma levels of Aß1-42 on peripheral mononuclear macrophage. Our results showed that in the early stage of Tg mice (7 months) and Pa (Wt-Tg) mice (4 months), the proportions of pro-inflammatory macrophages in peritoneal cavity, myeloid derived suppressor cells (MDSCs) in spleen, granulocyte-monocyte progenitors (GMPs) in bone marrow, and the plasma levels of interleukin-6 (IL-6) were significantly decreased. While the proportions of pro-inflammatory macrophages, MDSCs, GMPs, and the plasma levels of IL-6 and tumor necrosis factor (TNF)-α, as well as the numbers of bone marrow-derived macrophages (BMDMs) in mice brain were increased in the late stage of Tg mice (11 months) and Pa (Wt-Tg) mice (8 months). In addition, the proportions of monocytes in spleen and the proliferation of bone marrow cells (BMCs) were enhanced consistently, and the phagocytic function of macrophages kept stably after high plasma levels of Aß1-42 sustaining stimulation. These results demonstrated that high plasma levels of Aß1-42 play a biphasic regulating role at different stages of the disease, namely inhibiting effects on peripheral pro-inflammatory macrophages in the early stage of AD model, while promoting effects in the late stage of AD model. The mechanism behind this may be associated with their effects on MDSCs in spleen and myeloid progenitor cells in bone marrow. Therefore, intervening the effects of plasma Aß1-42 on pro-inflammatory macrophages might offer a new therapeutic approach to AD.

Current status of Guillain-Barré syndrome (GBS) in China: a 10-year comprehensive overview.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy; a disease involving the peripheral nervous system which is the most common cause of acute flaccid paralysis worldwide. So far, it is still lack of a comprehensive overview and understanding of the national epidemiological, clinical characteristics, and the risk factors of GBS in China, as well as differences between China and other countries and regions in these respects. With the global outbreak of the coronavirus disease 2019 (COVID-19), an epidemiological or phenotypic association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and GBS has attracted great attention. In this review, we outlined the current clinical data of GBS in China by retrieving literature, extracting and synthesizing the data of GBS in China from 2010 to 2021. Besides, we compared the characteristics of epidemiology, preceding events and clinical profiles of GBS between China and other countries and regions. Furthermore, in addition to conventional intravenous immunoglobulin (IVIG) and plasma exchange (PE) therapy, the potential therapeutic effects with novel medications in GBS, such as complement inhibitors, etc., have become the research focus in treatments. We found that epidemiological and clinical findings of GBS in China are approximately consistent with those in the International GBS Outcome Study (IGOS) cohort. We provided an overall picture of the present clinical status of GBS in China and summarized the global research progress of GBS, aiming to further understand the characteristics of GBS and improve the future work of GBS worldwide, especially in countries with the middle and low incomes.

Is there a causal nexus between COVID-19 infection, COVID-19 vaccination, and Guillain-Barré syndrome?

Guillain-Barré syndrome (GBS) is an immune-mediated inflammatory polyradiculoneuropathy, which commonly leads to a very high level of neurological disability. Especially, after the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causation between GBS and SARS-CoV-2 infection and the coronavirus disease 2019 (COVID-19) vaccination have aroused widespread concern. In the review, we analyzed the impacts of SARS-CoV-2 infection and COVID-19 vaccination on GBS globally, aiming to further understand the characteristics of GBS associated with COVID-19. Based on the electrophysiological data, patients suffering from GBS related to COVID-19 manifested as an acute inflammatory demyelinating polyneuropathy (AIDP). Moreover, we summarized the current findings, which may evidence GBS linking to SARS-CoV-2 infection and COVID-19 vaccination, and discussed the underlying mechanisms whether and how the SARS-CoV-2 virus and COVID-19 vaccination can induce GBS and its variants.

Association of lower liver function with cognitive impairment in the Shenzhen ageing-related disorder cohort in China.

Background: Accumulating evidence suggests that alterations in liver function may play an important role in the pathogenesis of Alzheimer's disease (AD). However, it remains unclear whether there is any relationship between lower liver function and cognitive impairment among the elderly. Methods: From 2017 to 2018, we recruited 7,201 older people (over 60 years old) from 51 community health centers in the Luohu District of Shenzhen City. According to the Mini-Mental State Examination (MMSE) score and education level, participants were divided into a cognitive impairment group (n = 372) and a normal cognitive function group (n = 6,829). Nonparametric test, chi-square tests, and binary logistic regression were used to analyze the data. Results: Cognitive impairment group exhibits older age, more female sex, lower education level, and lower levels of albumin and triglyceride. Additionally, the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio was mainly distributed in the range of 1.17 to 1.3 in the cognitive impairment group, and 0.85 to 1.00 in the normal cognitive function group (χ2 = 10.02, p = 0.04). Binary logistic regression showed that cognitive impairment was significantly associated with age (OR = 0.934, 95%CI: 0.886-0.985, p = 0.017), female sex (OR = 2.255, 95%CI: 1.761-2.888, p < 0.001), lower education level (less than senior high school) (OR = 11.509, 95%CI: 9.064-14.613, p < 0.001), and lower albumin (OR = 1.023, 95%CI: 1.004-1.043, p = 0.011). Conclusion: Except for age, female sex, and lower education level, lower level of albumin and elevated AST to ALT ratio correlate with cognitive impairment. Whether lower liver function plays a role in AD needs to be further studied.

The prediction effects of thyroid function in the severity of Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated inflammatory disorder affecting the peripheral nervous system (PNS), is usually complicated with autoimmune diseases including thyroid diseases. Herein, we explored roles of thyroid function and thyroid autoantibodies in the disease severity and its short-term prognosis of GBS. In addition, we further investigated the predictive value of thyroid function for GBS respiratory insufficiency. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 219 GBS patients. According to the thyroid function, the enrolled subjects were divided into 2 groups, that is, patients with abnormal thyroid function (case group) and those with normal thyroid function (control group). The clinical characteristics, disease severity, and short-term prognosis of the patients in 2 groups were compared. In addition, we also divided the 219 GBS patients into mechanical ventilation (MV) group and non-MV group according to whether MV was performed within 1 week after admission. The clinical characteristics, disease severity, short-term prognosis, Erasmus GBS respiratory insufficiency score (EGRIS), and the thyroid function were compared in the two groups. RESULTS: We found that GBS patients with abnormal thyroid function had longer duration of hospitalization, higher frequency of cranial nerve damage, and higher incidence of weakened tendon reflexes. Medical Research Council (MRC) scores on admission, at nadir, and at discharge were lower, and Hughes Functional Grading Scale (HFGS) scores on admission and at discharge were higher in GBS patients with abnormal thyroid function group. More patients in the abnormal thyroid function group had myelin, axonal, and myelin-axonal injuries. In the MV group, the time from onset to admission, MRC scores on admission, and the levels of free triiodothyronine (FT3) were lower; the levels of thyroglobulin antibody (TgAb) and EGRIS were significantly higher than those in the non-MV group. The combination of EGRIS and FT3 serum levels to predict GBS patients with MV, the area under the curve (AUC) was 0.905 (95% CI: 0.861 to 0.948, P < 0.05), sensitivity was 88.9%, and specificity was 84.7%. CONCLUSION: Our results suggest that the serum FT3 levels are negatively correlated with disease severity; the serum FT3 might be a biomarker for the incidence and severity of GBS. Both EGRIS and serum FT3 have a predictive value for the occurrence of acute respiratory insufficiency in GBS patients, and the combination of these two indicators can more accurately predict the risk of acute respiratory insufficiency in GBS patients.

Carotid Intraplaque Neovascularization and Future Vascular Events in Patients With Asymptomatic Carotid Stenosis.

Objective: Intraplaque neovascularization is a marker of plaque vulnerability and is used to predict the risk of future vascular events in patients with symptomatic carotid stenosis; however, its association with asymptomatic carotid stenosis has not been prospectively evaluated. Therefore, this study aimed to explore the association between intraplaque neovascularization assessed using contrast-enhanced ultrasound and the occurrence of future ischemic events in asymptomatic patients diagnosed with carotid stenosis. Methods: We recruited patients with asymptomatic carotid stenosis from our center. Contrast-enhanced ultrasound was performed at baseline. The outcomes were ischemic stroke and cardiovascular events. We plotted Kaplan-Meier survival curves and performed a log-rank test to compare endpoint event probability in patients with and without grade 2 intraplaque neovascularization. Univariate and multivariate Cox proportional hazards models were used to assess predictors of future vascular events. Results: The data of 50 participants were included in the analysis (median follow-up, 43.7 months). Endpoint events occurred in 12 participants (24%). The Kaplan-Meier survival curves showed that patients with grade 2 intraplaque neovascularization had a higher probability of future vascular events than those with grades 0 and 1 (p < .05). Grade 2 intraplaque neovascularization (hazard ratio: 4.530, 95% confidence interval, 1.337-15.343, p < .05) was an independent predictor of future vascular events in patients with asymptomatic carotid stenosis. Conclusion: Grade 2 intraplaque neovascularization assessed using contrast-enhanced ultrasound independently predicted future ischemic events in patients with asymptomatic carotid stenosis, and contrast-enhanced ultrasound may be an effective screening method to identify high-risk subgroups of patients with asymptomatic carotid stenosis.

Risk Factors for Mechanical Ventilation in Patients with Guillain-Barré Syndrome.

BACKGROUND: Respiratory support is required in 20-30% of patients with Guillain-Barré syndrome (GBS). We investigated clinical and biological risk factors for mechanical ventilation (MV) in northeast China through a retrospective GBS study. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) is a prognostic model for MV in patients with GBS, and its usefulness has been validated in several countries but not in China. Therefore, we intended to validate the EGRIS model in our GBS cohort. METHODS: A total of 252 patients with GBS were included in this study from January 2013 to October 2017. Risk factors for MV were identified via multivariate logistic regression analysis. The prognostic value of the EGRIS was validated via receiver operating characteristic curve analysis. RESULTS: Thirty-one patients (12.3%) required MV (mean age 54.19 years), with a majority being male (77.4%). The risk factors for MV were male sex [odds ratio (OR) 3.720, 95% confidence interval (CI) 1.155-11.985, p < 0.05], shorter interval from onset to admission (OR 0.830, 95% CI 0.711-0.970, p < 0.05), lower Medical Research Council sum score at admission (OR 0.942, 95% CI 0.911-0.973, p < 0.001), neutrophil-to-lymphocyte ratio at admission (OR 1.174, 95% CI 1.049-1.315, p < 0.01), and cranial nerve deficit (OR 3.805, 95% CI 1.373-10.541, p < 0.05). The EGRIS had a good predictive ability for MV (area under the receiver operating curve 0.861) in patients with GBS, and a high EGRIS was a predictor for MV (OR 8.778, 95% CI 3.432-22.448, p < 0.001). However, there was no significant difference in ganglioside administration between ventilated and nonventilated patients. CONCLUSIONS: An elevated neutrophil-to-lymphocyte ratio at admission and a high EGRIS could serve as predictors for MV in our GBS cohort.

Microbiota-gut-brain axis and Alzheimer's disease: Implications of the blood-brain barrier as an intervention target.

The microbiota-gut-brain axis has emerged as a focal point of biomedical research. Alterations of gut microbiota are involved in not only various immune/inflammatory disorders but also neurological disorders including Alzheimer's disease (AD). The initial stage of the involvement of gut microbiota in the pathogenesis of AD may be the dysfunction of the blood-brain barrier (BBB). Gut microbiota-derived products in the circulation can worsen the BBB integrity, easily cross the disrupted BBB and enter the brain to promote pathological changes in AD. In this review, we first summarize the current evidence of the associations among gut microbiota, AD, and BBB integrity. We then discuss the mechanism of gut microbiota on BBB dysfunction with a focus on bacteria-derived lipopolysaccharide and exosomal high-mobility group box 1. Novel insights into the modification of the BBB as an intervention approach for AD are highlighted as well.

Carotid intraplaque neovascularisation as a predictive factor for future vascular events in patients with mild and moderate carotid stenosis: an observational prospective study.

BACKGROUND: Intraplaque neovascularisation (IPN) increases the vulnerability of plaques, which makes them more likely to rupture and increases the risk of vascular events. However, it is unclear whether IPN can predict future vascular events (stroke recurrence and cardiovascular events). Previous studies on IPN have focused on patients with severe stenosis but overlooked patients with mild and moderate stenosis. This study aimed to investigate whether IPN assessed by contrast-enhanced ultrasonography (CEUS) in patients with mild and moderate degrees of stenosis is associated with future vascular events. METHODS: One hundred and twenty-one patients participated in this study. 76 patients who met the inclusion and exclusion criteria were included in the final dataset of the study. IPN was graded from 0 to 2 according to the extent of the microbubbles assessed using CEUS. The degree of carotid stenosis was graded as mild, moderate, or severe. We recorded future vascular events during the follow-up. Univariate and multivariate logistic regression analyses were used to evaluate risk factors for future vascular events. RESULTS: After a follow-up period of 30 ± 6 months, 30 patients (39.5%) experienced subsequent vascular events. Compared with the 'non-recurrent' group, the 'recurrent' group showed a higher proportion of grade 2 neovascularisation (p < 0.05), and it was an independent predictor of subsequent vascular events (odds ratio 6.066, 95% confidence interval 1.565-23.512, p < 0.05). Furthermore, in patients with mild and moderate stenosis, future vascular events occurred in an unexpectedly high proportion (up to 42.9%). In the 'recurrent' group, 55% of patients with mild and moderate stenosis had grade 2 neovascularisation. CONCLUSION: IPN by CEUS was an independent predictor of future vascular events in patients with recent ischemic stroke, and the high proportion of neovascularisation in patients with mild and moderate stenosis requires more attention.

Nuclear factor kappa B inhibitor suppresses experimental autoimmune neuritis in mice via declining macrophages polarization to M1 type.

Guillain-Barré syndrome (GBS) is an acute inflammatory and immune-mediated demyelinating disease of the peripheral nervous system (PNS). Macrophages play a central role in its animal model, experimental autoimmune neuritis (EAN), which has been well accepted. Additionally, nuclear factor (NF)-κB inhibitors have been used to treat cancers and have shown beneficial effects. Here, we investigated the therapeutic effect of M2 macrophage and the NF-κB pathway's correlation with macrophage activation in EAN in C57BL/6 mice. We demonstrate that M2 macrophage transfusion could alleviate the clinical symptoms of EAN by reducing the proportion of M1 macrophage in the peak period, inhibiting the phosphorylation of NF-κB p65. The NF-κB inhibitor (BAY-11-7082) could alleviate the clinical symptoms of EAN and shorten the duration of symptoms by reducing the proportion of M1 macrophages and the expression of proinflammatory cytokines. Consequently, BAY-11-7082 exhibits strong potential as a therapeutic strategy for ameliorating EAN by influencing the balance of M1/M2 macrophages and inflammatory cytokines.